JW Wilson, R Djukanovic, PH Howarth and ST Holgate
Immunopharmacology Group, Southampton General Hospital, United Kingdom.

It is widely known that inhaled corticosteroids are highly efficacious in the prophylactic treatment of asthma, but the mechanism of this action is not known. In this study we have investigated the effect of 6 wk of therapy with inhaled beclomethasone dipropionate (BDP; daily dose 2,000 micrograms for 2 wk and 1,000 micrograms for 4 wk) in a group of symptomatic individuals with asthma on clinical and physiologic indices of disease activity and on T cell numbers and state of activation in peripheral blood and bronchoalveolar lavage (BAL). This course of treatment had a marked effect of improving all indices of disease activity including symptom scores, morning peak expiratory flow (PEF), variation in PEF, and methacholine PC20 (from a geometric mean of 0.62 to 4.6 mg/ml) but did not alter the total numbers of T cells, identified by the CD3 receptor, or the CD4+ and CD8+ subsets when analyzed in peripheral blood or BAL using flow cytometry. However, BDP treatment had a marked effect in reducing the expression of the activation markers CD25 and HLA-DR (p < 0.02) in T cells recovered by BAL in which these markers were upregulated. A small but significant (p < 0.02) downregulation of HLA-DR expression was also observed on peripheral blood T cells. These data add to the view that T cells are upregulated in the airways of individuals with asthma and are susceptible to inhibition by topical corticosteroids.

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